4-Methylmorpholine → HCID 57436518, compound

HRID 502579Notes

Reaction equation

HRID 502579 reaction equation
[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.C(P(=O)(OCC)OCC)#N.CN1CCOCC1.[NH2:28][CH2:29][CH2:30][CH2:31][NH:32][C:33]1[C:37]2[CH:38]=[CH:39][C:40]([S:42]([NH:45][C:46]([CH3:49])([CH3:48])[CH3:47])(=[O:44])=[O:43])=[CH:41][C:36]=2[S:35][N:34]=1>C(Cl)Cl>[C:46]([NH:45][S:42]([C:40]1[CH:39]=[CH:38][C:37]2[C:33]([NH:32][CH2:31][CH2:30][CH2:29][NH:28][C:6](=[O:8])[C:5]3[CH:4]=[CH:3][C:2]([I:1])=[CH:10][CH:9]=3)=[N:34][S:35][C:36]=2[CH:41]=1)(=[O:44])=[O:43])([CH3:49])([CH3:47])[CH3:48]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 120854-Iodobenzoic acidHCID 76257Diethyl cyanophosphonateHCID 57436515HCID 57436515, compound

Product 1

HCID 57436518HCID 57436518, compoundYield 62.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 4-iodobenzoic acid (181 mg, 0.7 mmol) in methylene chloride (2 mL), diethyl cyanophosphonate (115 μL, 0.8 mmol) and 4-methylmorpholine (160 μL, 1.5 mmol) were added at room temperature and allowed to stir for 15 min. A solution of 3-(3-aminopropylamino)-N-tert-butylbenzo[d]isothiazole-6-sulfonamide (238 mg, 0.7 mmol) in methylene chloride (4 mL) was then added and the resulting reaction mixture was allowed to stir overnight. The reaction mixture with diluted with methylene chloride (20 mL), washed with 10% HCl aqueous solution and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with 1:1 ethyl acetate:hexanes provided N-(3-(6-(N-tert-butylsulfamoyl)benzo[d]isothiazol-3-ylamino)propyl)-4-iodobenzamide (252 mg). 1H NMR (300 MZh, CDCl3): 8.47 (d, 1H), 7.96 (dd, 1H), 7.86 (d, 1H), 7.82 (d, 2H), 7.60 (d, 2H), 7.37 (t, 1H), 6.19 (br s, 1H), 4.98 (s, 1H), 3.75 (t, 2H), 3.60 (dd, 2H), 2.02 (q, 2H), 1.29 ppm (s, 9H). 13C NMR (CDCl3): 167.25, 159.79, 154.96, 139.87, 138.01, 134.16, 128.91, 126.28, 121.54, 121.19, 98.76, 55.46, 43.08, 40.33, 37.32, 30.66, 30.06. MW=572 confirmed by LC-MS, tr=14.28 min (Method Y) MH+=573.

Workup

  1. customthe resulting reaction mixture
  2. stirringto stir overnight
  3. washwashed with 10% HCl aqueous solution and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography
  8. washon silica gel, eluting with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-92749ef136144d368337ff6a29dbed46
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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